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Designing Engineered Stem Cell Therapies for Immune-Mediated Demyelinating Diseases

Award Number: F31AI197938
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/22/2026
PERIOD OF PERFORMANCE END DATE: 12/21/2027

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Designing Engineered Stem Cell Therapies for Immune-Mediated Demyelinating Diseases - Multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are immune-mediated demyelinating diseases that impact close to 5 million people worldwide. White matter plaque formation leads to acute inflammation, chronic demyelination, and axonal loss. These inflammatory lesions predominantly consist of T lymphocytes and reactive microglia, which lead to the breakdown of the protective myelin sheath coating on axons and the destruction of oligodendrocytes. This degradation leads to the release of myelin oligodendrocyte glycoprotein (MOG) and other proteins expressed on the outermost later of the myelin sheath into the lesion microenvironment. With the recent explosion of biologics and immunotherapy, new treatment options have become available for MS but remain limited for MOGAD. However, while these therapies are effective at reducing the frequency of relapses, there are risks associated with long-term systemic immunosuppression and in many patients, their disease eventually progresses. Therefore, the overall goal of this proposal is to develop novel, safe, and effective treatments and strategies that can specifically modulate the immune response in MS and MOGAD. Mesenchymal stem cells (MSCs) are characterized by their immunosuppressive and regenerative properties. As such, adoptive transfer of MSCs has been investigated as an independent therapeutic option in immune-mediated diseases and was recently FDA approved in pediatric graft-versus-host disease. MSCs mediate their immunosuppressive capabilities at least partly through the secretion of immunosuppressive cytokines, such as interleukin (IL)-10. IL-10 is a potent anti-inflammatory cytokine that inhibits the synthesis of IL-2 and interferon-ɣ, two cytokines crucial for T cell development and activation. IL-10 is also reported to have neuroprotective effects by inhibiting astrocyte activation and preventing accumulation of the excitatory neurotransmitter glutamate. Previous studies have implicated that engineering MSCs with designer chimeric antigen receptors (CARs) results in enhanced trafficking to sites of inflammation and augmented immunosuppressive capabilities. This leads to our central hypothesis that engineering MSCs to express MOG-targeting CARs that secrete IL-10 (MOG-CAR-IL10) can ameliorate treatment-refractory MS and MOGAD. This hypothesis will be tested by pursuing two specific aims: Aim 1 will study trafficking of MOG-CAR-IL10 to the central nervous system in mouse models of T-cell mediated demyelination and Aim 2 will determine the immunosuppressive effects of MOG-CAR-IL10 on MS in preclinical models. By the completion of this work, we expect to have defined how MOG-CAR-IL10 interacts with T cells in MS and MOGAD and to have developed novel targeted cellular engineering therapies to ameliorate treatment-refractory MS and MOGAD more effectively. This proposal will allow me to acquire cross-disciplinary training in (i) mouse modeling, (ii) vector design and cell engineering, (iii) MSC-immune cell functional interactions, and (iv) translational science.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $50,114 )
2026	2026	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	000	1	6/23/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Designing Engineered Stem Cell Therapies for Immune-Mediated Demyelinating Diseases

Award Number: F31AI197938

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/22/2026

PERIOD OF PERFORMANCE END DATE: 12/21/2027

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